Gu Minzhi, Ren Bo, Fang Yuan, Ren Jie, Liu Xiaohong, Wang Xing, Zhou Feihan, Xiao Ruiling, Luo Xiyuan, You Lei, Zhao Yupei
Department of General Surgery Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing P. R. China.
Key Laboratory of Research in Pancreatic Tumor Chinese Academy of Medical Sciences Beijing P. R. China.
MedComm (2020). 2024 Feb 19;5(2):e495. doi: 10.1002/mco2.495. eCollection 2024 Feb.
Epigenetic modifications are defined as heritable changes in gene activity that do not involve changes in the underlying DNA sequence. The oncogenic process is driven by the accumulation of alterations that impact genome's structure and function. Genetic mutations, which directly disrupt the DNA sequence, are complemented by epigenetic modifications that modulate gene expression, thereby facilitating the acquisition of malignant characteristics. Principals among these epigenetic changes are shifts in DNA methylation and histone mark patterns, which promote tumor development and metastasis. Notably, the reversible nature of epigenetic alterations, as opposed to the permanence of genetic changes, positions the epigenetic machinery as a prime target in the discovery of novel therapeutics. Our review delves into the complexities of epigenetic regulation, exploring its profound effects on tumor initiation, metastatic behavior, metabolic pathways, and the tumor microenvironment. We place a particular emphasis on the dysregulation at each level of epigenetic modulation, including but not limited to, the aberrations in enzymes responsible for DNA methylation and histone modification, subunit loss or fusions in chromatin remodeling complexes, and the disturbances in higher-order chromatin structure. Finally, we also evaluate therapeutic approaches that leverage the growing understanding of chromatin dysregulation, offering new avenues for cancer treatment.
表观遗传修饰被定义为基因活性的可遗传变化,这些变化不涉及潜在DNA序列的改变。致癌过程是由影响基因组结构和功能的改变积累所驱动的。直接破坏DNA序列的基因突变,辅以调节基因表达的表观遗传修饰,从而促进恶性特征的获得。这些表观遗传变化的主要方面是DNA甲基化和组蛋白标记模式的改变,它们促进肿瘤的发展和转移。值得注意的是,与基因变化的永久性相反,表观遗传改变的可逆性使表观遗传机制成为发现新型治疗方法的主要靶点。我们的综述深入探讨了表观遗传调控的复杂性,探索其对肿瘤发生、转移行为、代谢途径和肿瘤微环境的深远影响。我们特别强调表观遗传调控各层面的失调,包括但不限于负责DNA甲基化和组蛋白修饰的酶的异常、染色质重塑复合物中的亚基缺失或融合,以及高阶染色质结构的紊乱。最后,我们还评估了利用对染色质失调日益深入的理解的治疗方法,为癌症治疗提供了新途径。
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